METHODS: The ASSERT study was a phase 3, double-blind, randomised, placebo-controlled trial that enrolled patients at 21 medical centres or hospitals in ten countries (Belgium, France, Germany, Italy, Malaysia, the Netherlands, Poland, Türkiye, the UK, and the USA). Eligible patients had a genetically confirmed diagnosis of Alagille syndrome, a history of significant pruritus, and elevated serum bile acids. Patients were randomly assigned (2:1) to receive oral odevixibat 120 μg/kg per day or placebo for 24 weeks (in a block size of six and stratified by age: <10 years and ≥10 years to <18 years) via a web-based system. Patients, clinicians, study staff, and people analysing the data were masked to treatment allocation. The primary efficacy endpoint was change in caregiver-reported scratching score (on the PRUCISION instrument; range 0-4) from baseline to weeks 21-24. The prespecified key secondary efficacy endpoint was change in serum bile acid concentration from baseline to the average of weeks 20 and 24. Outcomes were analysed in patients who received at least one dose of study drug (the full analysis set for efficacy outcomes and the safety analysis set for safety outcomes). This trial is registered on ClinicalTrials.gov (NCT04674761) and EudraCT (2020-004011-28), and is completed.
FINDINGS: Between Feb 26, 2021, and Sept 9, 2022, 52 patients were randomly assigned to receive odevixibat (n=35) or placebo (n=17), all of whom were included in the analysis sets. The median age was 5·5 years (IQR 3·2 to 8·9). 27 (52%) of 52 patients were male and 25 (48%) were female. The mean scratching score was elevated at baseline in both groups (2·8 [SD 0·5] for odevixibat vs 3·0 [0·6] for placebo). Mean scratching scores at weeks 21-24 were 1·1 (0·9) for odevixibat and 2·2 (1·0) for placebo, representing a least-squares (LS) mean change of -1·7 (95% CI -2·0 to -1·3) for odevixibat and -0·8 (-1·3 to -0·3) for placebo, which was significantly greater for odevixibat than for placebo (difference in LS mean change from baseline -0·9 [95% CI -1·4 to -0·3]; p=0·0024). Odevixibat also resulted in significantly greater reductions in mean serum bile acids from baseline versus placebo (237 μmol/L [SD 115] with odevixibat vs 246 μmol/L [121] with placebo) to the average of weeks 20 and 24 (149 μmol/L [102] vs 271 μmol/L [167]; LS mean change -90 μmol/L [95% CI -133 to -48] with odevixibat vs 22 μmol/L [-35 to 80] with placebo; difference in LS mean change -113 μmol/L [95% CI -179 to -47]; p=0·0012). The most common treatment-emergent adverse events were diarrhoea (ten [29%] of 35 patients in the odevixibat group vs one [6%] of 17 in the placebo group) and pyrexia (eight [23%] vs four [24%]). Seven patients had serious treatment-emergent adverse events during the treatment period: five (14%) in the odevixibat group and two (12%) in the placebo group. No patients discontinued treatment and there were no deaths.
INTERPRETATION: Odevixibat could be an efficacious non-surgical intervention to improve pruritus, reduce serum bile acids, and enhance the standard of care in patients with Alagille syndrome. Longer-term safety and efficacy data of odevixibat in this population are awaited from the ongoing, open-label ASSERT-EXT study.
FUNDING: Albireo Pharma, an Ipsen company.
METHODS: A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12.
RESULTS: The agreement between capillary and laboratory venous blood was moderate (0.64-0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively.
CONCLUSIONS: The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions.
METHODS: A web-based cross-sectional survey was conducted between 12th and May 13, 2020. Quota sampling was used to attain equal gender and age distributions representative of the Japanese population.
RESULTS: A total of 4127 complete responses were analysed. Higher educational level (B = 0.045, p = 0.002) and household income (B = 0.04, p = 0.009) were associated with a higher increase in preventive measures when comparing before and after the state of emergency was declared. The highest reported social anxiety was a feeling of fear (65.6%), followed by embarrassment (43.8%), keeping infection a secret (41.3%), avoidance (41.3%), and stigma (25.5%). A total of 86.1% of the respondents reported moderate to severe anxiety. The partial least square-based structural equation modelling (PLS-SEM) revealed that being female has the greatest effect (B = 0.246, p
METHODS: We analyzed Global Burden of Disease Study 2017 data on the prevalence of childhood epilepsy, intellectual disability, and vision or hearing loss and on years lived with disability (YLD) derived from systematic reviews, health surveys, hospital and claims databases, cohort studies, and disease-specific registries. Point estimates of the prevalence and YLD and the 95% uncertainty intervals (UIs) around the estimates were assessed.
RESULTS: Globally, 291.2 million (11.2%) of the 2.6 billion children and adolescents (95% UI: 249.9-335.4 million) were estimated to have 1 of the 4 specified disabilities in 2017. The prevalence of these disabilities increased with age from 6.1% among children aged <1 year to 13.9% among adolescents aged 15 to 19 years. A total of 275.2 million (94.5%) lived in low- and middle-income countries, predominantly in South Asia and sub-Saharan Africa. The top 10 countries accounted for 62.3% of all children and adolescents with disabilities. These disabilities accounted for 28.9 million YLD or 19.9% of the overall 145.3 million (95% UI: 106.9-189.7) YLD from all causes among children and adolescents.
CONCLUSIONS: The number of children and adolescents with these 4 disabilities is far higher than the 2004 estimate, increases from infancy to adolescence, and accounts for a substantial proportion of all-cause YLD.
METHODS: A dataset of 1576 online survey responses yielded subsamples for anorexia nervosa (n = 155), bulimia nervosa (n = 55), binge eating disorder (n = 33), other specified feeding or eating disorder (n = 93), and healthy participants (n = 505). The hierarchical linear regression analysis included Eating Disorder Examination Questionnaire 6.0 Global Score as the dependent variable; Young Positive Schema Questionnaire, Emotional Regulation Questionnaire, and Cognitive Flexibility Inventory subscale scores as the independent variables; and demographic measures as the covariates.
RESULTS: The number of significant predictors varied considerably by ED sub-group. Amongst the anorexia nervosa, bulimia nervosa, and healthy subsamples, the adaptive schema Self-Compassion and Realistic Expectations was associated with lower ED symptom severity. In comparison, age and body mass index were the strongest predictors for binge eating disorder, whilst the Expressive Suppression (a subscale of the Emotional Regulation Questionnaire) was the strongest predictor for other specified feeding or eating disorders.
CONCLUSION: Early adaptive schemas, cognitive flexibility, and emotional regulation vary across ED subtype, suggesting the need for tailored treatment that disrupts the self-reinforcing cycle of ED psychopathology. Future research investigating how early adaptive schemas may predict or be associated with treatment response across diagnostic subtypes is needed.
LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time-series with or without the intervention, such as case studies.
OBJECTIVE: To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.
METHODS: This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients' socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis.
RESULTS: High degree of drug resistance (median 5 drugs, range 2-8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR=1.953, p=0.034) and public private mix (OR=2.824, p=0.046) sectors were predictors of ofloxacin resistance.
CONCLUSION: The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public-private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.
METHODS: A cross-sectional study used to collect the data via an online cross using a form created from a google questionnaire forms. A total of 1,802 respondents were gathered at a single point in time. The authors used the Health Belief Model (HBM) approach to measure and create a model for the prevention of local transmission of COVID-19.
RESULTS: This study found that more than half of the respondents still had low perceived susceptibility (16%) and severity (43%). There were only 3% respondents with perceived barriers and 19% with strong self-efficacy. The findings showed that self-efficacy and perceived barriers had statistically significant relationships with preventive behavior (p-value <0.05). The goodness of fit index showed that the proposed model was not fit for the data (RMSE<0.080, GFI>0.950, AGFI>0.950, SRMR<0.100), which means that it was not fit to describe the empirical phenomenon under study.
CONCLUSIONS: This study found that more than half of the respondents still had low perceived susceptibility (84%) and severity (67%), but more than half had high perceived benefits (54%). Only a few respondents had significant barriers to implementing COVID-19 transmission prevention behaviours (3%). Still, most respondents had low perceived self-efficacy (81%), and only 60% had good behaviours related to COVID-19 prevention. In the context of COVID-19 preventive behaviour, we recommended to improve perceived susceptibility and severity by providing the correct information (which contain information about how people susceptible to the virus and the impact of infected by the virus) with the local cultural context.
METHODS: This cross-sectional study was conducted during Phase Four of Malaysia's National Recovery Plan and examines how the pandemic has affected health behaviors among adult Malaysians. The study gathered data online using convenience sampling with 1,004 respondents aged 18 and above. The research focused on diverse health domains, including eating habits, physical activity, smoking, alcohol consumption, and sleep patterns. The Wilcoxon Signed Rank test and descriptive statistics were employed to compare health behaviors before and after COVID-19.
RESULTS: Findings indicate noteworthy shifts in eating behaviors, with increased water and fruit consumption (p